scholarly journals Regulation of drug transporter expression by oncostatin M in human hepatocytes

2011 ◽  
Vol 82 (3) ◽  
pp. 304-311 ◽  
Author(s):  
Marc Le Vee ◽  
Elodie Jouan ◽  
Bruno Stieger ◽  
Valérie Lecureur ◽  
Olivier Fardel
Keyword(s):  
Human Hepatocytes ◽  
Oncostatin M ◽  
Drug Transporter ◽  
Transporter Expression

scholarly journals Drug Transporter Expression and Localization in Rat Nasal Respiratory and Olfactory Mucosa and Olfactory Bulb: Fig. 1.

2010 ◽  
Vol 38 (10) ◽  
pp. 1644-1647 ◽  
Author(s):  
Mary Beth Genter ◽  
Mansi Krishan ◽  
Lisa M. Augustine ◽  
Nathan J. Cherrington
Keyword(s):  
Olfactory Bulb ◽  
Olfactory Mucosa ◽  
Drug Transporter ◽  
Transporter Expression

scholarly journals Modeling Human Nonalcoholic Steatohepatitis-Associated Changes in Drug Transporter Expression Using Experimental Rodent Models

2014 ◽  
Vol 42 (4) ◽  
pp. 586-595 ◽  
Author(s):  
Mark J. Canet ◽  
Rhiannon N. Hardwick ◽  
April D. Lake ◽  
Anika L. Dzierlenga ◽  
John D. Clarke ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Rodent Models ◽  
Drug Transporter ◽  
Transporter Expression

scholarly journals Transporter Gene Regulation in Sandwich Cultured Human Hepatocytes Through the Activation of Constitutive Androstane Receptor (CAR) or Aryl Hydrocarbon Receptor (AhR)

2021 ◽  
Vol 11 ◽  
Author(s):  
Congrong Niu ◽  
Bill Smith ◽  
Yurong Lai
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Constitutive Androstane Receptor ◽  
Gene Induction ◽  
Human Hepatocytes ◽  
Drug Transporter ◽  
Transporter Gene ◽  
Aryl Hydrocarbon ◽  
Multiple Donors ◽  
Metabolizing Enzyme ◽  
Nuclear Receptor Ligands

The induction potentials of ligand-activated nuclear receptors on metabolizing enzyme genes are routinely tested for new chemical entities. However, regulations of drug transporter genes by the nuclear receptor ligands are underappreciated, especially in differentiated human hepatocyte cultures. In this study, gene induction by the ligands of constitutive androstane receptor (CAR) and aryl hydrocarbon receptor (AhR) was characterized in sandwich-cultured human hepatocytes (SCHH) from multiple donors. The cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole (OP), 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO) and phenobarbital (PB) for three days. RNA samples were analyzed by qRT-PCR method. As expected, CITCO, the direct activator, and PB, the indirect activator of CAR, induced CYP3A4 (31 and 40-fold), CYP2B6 (24 and 28-fold) and UGT1A1 (2.9 and 4.2-fold), respectively. Conversely, TCDD and OP, the activators of AhR, induced CYP1A1 (38 and 37-fold), and UGT1A1 (4.3 and 5.0-fold), respectively. In addition, OP but not TCDD induced CY3A4 by about 61-fold. Twenty-four hepatic drug transporter genes were characterized, and of those, SLC51B was induced the most by PB and OP by about 3.3 and 6.5 fold, respectively. Marginal inductions (about 2-fold) of SLC47A1 and SLCO4C1 genes by PB, and ABCG2 gene by TCDD were observed. In contrast, SLC10A1 gene was suppressed about 2-fold by TCDD and CITCO. While clinical relevance of SLC51B gene induction or SLC10A1 gene suppression warrants further investigation, the results verified that the assessment of transporter gene inductions are not required for new drug entities, when a drug does not remarkably induce metabolizing enzyme genes by CAR and AhR activation.

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